In spite of the extensive use of indirect anticoagulants in medicine, their mechanism of action is unknown. It has been assumed that coumarin anticoagulants compete with vitamin K for an active site, but recent evidence suggests that the locus of action of anticoagulants may be on the metabolism of vitamin K. Vitamin K1 is converted in the liver to vitamin K1 epoxide, which is rapidly reduced back to the vitamin. There are a number of observations which indicate that the K1-epoxide cycle is involved in the inhibition of prothrombin synthesis by anticoagulants. We will determine if impairment of either the epoxidation or reduction step of the cycle is correlated with inhibition of clotting protein synthesis. We will also determine if any of the numerous clinical drug interactions with coumarins are due to effects on the metabolism of the vitamin.